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Biomedical subjects

Y Katsuki

Publications and source records attributed to Y Katsuki.

At least 19 recordsLinked to original sources

Synergistic stimulation of nitric oxide hemoglobin production in rats by recombinant interleukin 1 and tumor necrosis factor.

Nitric oxide (NO) is formed from arginine in Escherichia coli lipopolysaccharide (LPS) treated rat; however, none of specific cytokine inducing NO generation is yet determined. We studied the effect of interleukin 1 (IL-1) and tumor necrosis factor (TNF) on NO production in rats by detecting NO-hemoglobin in their blood, using electron spin resonance. Either IL-1 or TNF alone stimulated NO-hemoglobin formation. Combined administration of IL-1 and TNF markedly enhanced NO-hemoglobin generation, demonstrating the synergistic character of both stimuli on NO production. Further, LPS and TNF in combination were more potent stimulator of NO-hemoglobin production in rats than each alone.

Animals

Spin trapping study on the kinetics of Fe2+ autoxidation: formation of spin adducts and their destruction by superoxide.

The oxidation of Fe2+ was investigated by electron spin resonance spin trapping techniques with N-t-butyl-alpha-phenylnitrone (PBN) and dimethyl sulfoxide. Under pure oxygen, the spin adduct PBN/.OCH3 was rapidly generated by the addition of Fe2+ (0.2-1.2 mM) into phosphate buffer containing ethylenediaminetetraacetate (EDTA), dimethyl sulfoxide, and PBN at pH 7.4, but it decayed. The decay process of PBN/.OCH3 consists of two components. The fast decay was dependent on Fe2+ concentration. Another was due to destruction of the spin adduct by superoxide anion (.O2-), because superoxide dismutase (SOD) markedly prevented the decay. Catalase decreased the yield of PBN/.OCH3. When EDTA was replaced by diethylenetriaminepentaacetic acid (DTPA), both the generation and decay process of PBN/.OCH3 were slow. SOD and catalase effects were similar to those in EDTA. Fe2+ produced PBN/.OCH3 even in the absence of chelators. We could estimate the kinetic parameters by computer simulation, comparing the Fe2+ oxidation in EDTA with that in DTPA. These results demonstrate that Fe2+ reacts with O2 to generate .O2- and then H2O2, which produces .CH3 by reaction with Fe2+ and dimethyl sulfoxide.(.)OCH3 results from the reaction between .CH3 and O2. The adduct PBN/.OCH3 decays by reaction with Fe2+ and .O2-.

Air

[Intraperitoneal cancer chemotherapy using an implantable reservoir in patients with peritonitis carcinomatosa].

Intraperitoneal cancer chemotherapy using an implantable reservoir has been recognized as an effective treatment. In this report, we evaluate treatment results in 20 cases undergoing this chemotherapy and the correlation between reservoir-use period and cumulative survival rates. Twenty patients with an average age of 59.3 years were all observed to have peritoneal dissemination during operations in the period of January 1987 through January 1991. Their primary diseases were 10 cases of gastric cancer, 8 cases of colorectal cancer, 1 case of appendiceal carcinoma, and 1 case of malignant tumor of retroperitoneum. Intraperitoneal reservoirs were implanted in surgically-made pockets in subcutaneous lower abdomen, and their catheters were inserted into Douglas cul de sac. Medications used were CDDP, MMC, and 5-FU. The average number of administration was about 6 or 7, but, the maximum number was 67 in one case. Contrast media or RI infused via reservoirs was recognized to diffuse widely within the peritoneal cavity. Eighteen of 20 cases (90%) obtained good conditions to undergo ambulant treatments. The longest survival records were 827 days in a gastric cancer group, 639 days in a colorectal cancer group, and 326 days in a malignant tumor of retroperitoneum group. Two cases having the former two survival records are still alive at this writing. One case with appendiceal carcinoma is PS 0 and now under out-patient treatment at 2 years and 6 months after operation. The 50% survival period, and 6-month, 1-year, and 2-year cumulative survival rates were 8.8 months, 60%, 40.5%, and 37%, respectively in the gastric cancer group; and 13.5 months, 75%, 63%, and 31.5%, respectively, in the colorectal cancer group. On the contrary, 50% using period, and 6-month, 1-year, and 2-year cumulative using rates were 5.3 months, 40%, 10%, and 10%, respectively, in the gastric cancer group; and 7.9 months, 58%, 0%, and 0%, respectively, in the colorectal cancer group. Evaluation of the correlation between the reservoir use periods and cumulative survival rates has led to the conclusion that cumulative survival rates are extended significantly p = 0.0011 in each cancer group with more than 6 months treatment period compared to within each cancer group with less than 6 months treatment. 1) Intraperitoneal cancer chemotherapy using an implantable reservoir enables patients to receive treatment at outpatient clinics. 2) The continuous treatment for more than 6 months suggests the possibility for longer survival.

Cisplatin

Mechanism of pharmacodynamic and pharmacokinetic interactions between acetohexamide and phenylbutazone in rabbits.

The interaction of acetohexamide (AH) with phenylbutazone (PBZ) was investigated in rabbits. Orally administered PBZ caused a potentiation of hypoglycaemic action after oral administration of AH. This can be explained by the fact that the co-administration of PBZ significantly increased both the serum concentrations of AH and its pharmacologically active metabolite. (-)-hydroxyhexamide [(-)-HH], after AH administration. The co-administration of PBZ decreased the renal clearance (Clr) and non-renal clearance (Clnr) of AH. PBZ inhibited the in vitro reduction of AH to (-)-HH and decreased the accumulation of (-)-HH by the kidney cortical slices. These results indicate that the mechanism of in vivo interaction of AH with PBZ is complicated.

Acetohexamide

[Evaluation of intraperitoneal cancer chemotherapy using an implantable reservoir in patients with peritonitis carcinomatosa].

We evaluated the clinical usefulness of intraperitoneal cancer chemotherapy using an implantable reservoir in patients with peritonitis carcinomatosa as compared with conventional chemotherapy. The cases were comprised of 9 gastric cancers, 6 colorectal cancers, 1 appendiceal carcinoma, and 1 malignant tumor of retroperitoneum, all of which were observed to have peritoneal dissemination during surgical operations. Medications infused were CDDP in 14 cases, MMC in 4 cases, and 5-FU in 1 case. The patients with P2 and P3 findings (group A) were compared with other cases treated with conventional chemotherapy (group B). The average survival periods were, for gastric cancer patients, 6 months in group A and 8.6 months in group B; for the colorectal cancer group, 10.5 months in group A and 13.6 months in group B. The 6-month and 1-year cumulative survival rates for the gastric cancer patients were 100% and 0%, respectively in group A; 52% and 17%, respectively in group B. For the colo-rectal cancer group, the 6-month, 1-year, and 2-year cumulative survival rates were 75%, 75%, and 0%, respectively, in group A; 79%, 45%, and 14% respectively, in group B. These results did not show significant differences between the two groups. On the other hand, the average outpatient clinic visiting rates in the gastric cancer patients in groups A and B showed a significant difference; 72.6% (group A) and 46.8% (group B). Also, the rates in the colo-rectal cancer patients showed a significant difference; 69.6% (group A) and 61.5% (group B). As a result, the extension of the period of stay at home and visiting of our outpatient clinic for treatment was obtained in the group A. Consequently, this intraperitoneal cancer chemotherapy using an implantable reservoir was extremely effective in patients with peritonitis carcinomatosa for outpatient treatment over the long term without loss of quality of life for each patient.

Adult

[Evaluation of long survival cases treated with intra-arterial cancer chemotherapy using implantable reservoirs].

We have treated unresectable liver tumor with intraarterial infusion chemotherapy using an implantable reservoir since 1983. Out of the total 44 cases receiving the chemotherapy during the period from 1983 to February 1989, the evaluation of 8 cases (18.2%) surviving over a year is reported. The 8 cases consist of 3 cases of primary hepatic cancer, 4 cases of metastatic hepatic cancer and 1 case of malignant hemangiopericytoma of pelvis. The cases of primary hepatic cancer are 2 cases of hepatoma (413, 420 days) and 1 case of cancer of bile-duct (400 days). The metastatic cases are 1 case of gastric cancer (826 days), 2 cases of colo-rectal cancer (698, 1080 days) and 1 cases of leiomyosarcoma of small intestine (577 days). A case of malignant hemangiopericytoma of pelvis has survived 4 years and 3 months after the infusion chemotherapy via the internal iliac artery. The two cases of colo-rectal cancer were treated with continuous infusion of FUDR via the proper hepatic artery using Infusaid. For the other cases, ADM and CDDP were infused repeatedly with single-shot type Infuse-a port. Intra-arterial infusion chemotherapy is very useful because treatment in the outpatient clinics is possible over the longterm, and it is possible for patients receiving the therapy to maintain quality of life.

Adult

[Genetic markers and thrombin reaction in a family of Bernard-Soulier syndrome].

A family with Bernard-Soulier syndrome (BSS) was investigated with reference to the genetic markers and thrombin reactions. The proband was a 24-year-old man with a life-long history of epistaxis and gingival bleeding. His parents were first cousins; furthermore, his father was born to parents of second cousins. His father also had bleeding tendency and was also diagnosed as having BSS. However, his mother and elder brother were normal. Genetic marker analysis among the family members suggested that the 16th chromosome was associated with the development of BSS, because only the haptoglobin genotype coded on the 16th chromosome was the marker in both the proband and his father. In addition, they both exhibited decreased thrombin-induced platelet aggregation at a low dose, but an almost normal reaction at a high dose of thrombin.

Adult

[Pharmacological studies of eicosapentaenoic acid ethylester (EPA-E) on high cholesterol diet-fed rabbits].

The effects of eicosapentaenoic acid ethylester (EPA-E) at daily doses of 3 and 30 mg/kg (p.o.) on vascular lesions and changes in blood components were investigated in rabbits fed with a 1% cholesterol diet for 12 weeks and partly compared with those given 30 mg/kg/day (p.o.) of ticlopidine. EPA-E at 30 mg/kg significantly improved the reduction in distensibility of isolated thoracic aorta caused by cholesterol diet feeding. Ticlopidine at 30 mg/kg also showed significant but milder improvement. EPA-E at 30 mg/kg, unlike ticlopidine, tended to lower cholesterol content in the thoracic wall and elastin fraction. Although EPA-E did not act on plasma total cholesterol, HDL-cholesterol and triglyceride contents, it tended to mildly reduce platelet aggregability in response to sodium arachidonate and the increased production of TXA2-like activity by platelets. In addition, daily doses of 30 mg/kg EPA-E caused a significant increase in plasma and platelet EPA-E contents without any change in docosahexaenoic acid and arachidonic acid contents. From these results, daily administration of EPA-E to cholesterol diet-fed rabbits caused a remarkable improvement of the reduction in distensibility of isolated thoracic aorta. The mechanism of this improvement by EPA-E appears to depend on the protection of elastic fibers from lipid deposition on the vascular wall.

Animals

[The effects of eicosapentaenoic acid ethyl ester (EPA-E) on arterial thrombosis in rabbits and vascular lesions in rats].

The effects of highly purified ethyl ester of eicosapentaenoic acid (EPA-E) on ellagic acid-induced thrombus formation in the stenosed femoral artery in rabbits and on the progression of laurate-induced vascular lesions in rats were examined. (1) EPA-E in single administration significantly prevented the thrombus formation induced by ellagic acid in the stenosed femoral artery of rabbits. (2) EPA-E restored the hypercoagulation activity at 5 min and 3 hr after the ellagic acid injection. Platelet aggregability induced by arachidonic acid decreased at 5 min and 3 hr after the ellagic acid injection; EPA-E had little effect on this change. EPA-E showed almost no effect on fibrinolytic activity, blood viscosity and filterability of washed red blood cells after the ellagic acid injection. (3) Moreover, EPA-E in daily administrations showed a significant preventative effect against the laurate-induced vascular lesions in rats. The efficacy of EPA-E on arterial thrombosis and vascular lesions observed in this study suggests that EPA-E is a candidate for the treatment of peripheral circulatory disturbance.

Animals

[Transarterial embolization in the treatment of hepatoma complicated with cirrhosis, esophageal varices and hypersplenism].

A case of hepatoma with cirrhosis for whom hepatectomy was impossible because of a severe complication is reported. The case has been treated with various treatments, so long survival has been obtained. The patient is a 56-year-old female with hepatoma with cirrhosis. The initial symptom was bleeding from esophageal varices. Her condition was not suitable for hepatectomy because of hypersplenism and remarkable hepatic disorder. Consequently, she was given endoscopic sclerotherapy for esophageal varices, partial splenic embolization for hypersplenism, and transarterial embolization with ADM, Lipiodol and Spongel powder for hepatoma. Although abdominal pain, pleural effusion and bleeding from gastric ulcer appeared after embolization, esophageal varices and hypersplenism were significantly improved; reduction of 75% of hepatoma was observed and AFP decreased from 18.7 ng to 3 ng. At 12 months after the embolization, there is no sign of hepatoma growth, rupture of esophageal varices or hypersplenism.

Carcinoma, Hepatocellular

Evidence for "response to injury" hypothesis.

Role of platelet-derived growth factor (PDGF) in myointimal thickening described in "response to injury" hypothesis was investigated with artery of rats in culture and with air-injured artery of rats. PDGF promoted cell growth in ring preparation of carotid artery in culture denuded with citrate. It did not promote any cell growth in preparations without denudation. Trapidil, a PDGF antagonist, inhibited the cell growth promoted by PDGF in the denuded arterial ring. Systemic injection of PDGF was performed for 8 days to rats with thrombocytopenia induced by injections of anti-platelet serum. This treatment caused myointimal thickening of carotid artery 10 days after denudation by means of air injury. Trapidil at oral intake levels of 1, 3 and 30 mg/kg/day inhibited this change observed in denuded site of artery. Trapidil at oral intake of 6 mg/kg/day also inhibited myointimal thickening observed 15 days after denudation of carotid artery by air injury in normotensive and spontaneous hypertensive rats both with normal platelet counts. These results evidenced the role of PDGF in myointimal thickening described in "response to injury" hypothesis and clinical use of trapidil may be a new approach to the treatment of atherosclerosis.

Animals

The chemical receptive mechanism in the lateral-line organ.

Stimulating effects of various mono- and divalent cations on the lateral-line organ were theoretically analysed by use of the site binding chemical adsorption model with the principle of "hard and soft acids and bases." A linear relation between the softness parameter and the logarithmic value of the intrinsic association constant was obtained for the cations of Na, K, Tl, Ag, Ca, Mg, and Cd. The order of effectiveness of these cations agreed with that of the intrinsic association constant. Using these values for various cations, the critical concentration of divalent cations necessary to supress the effect of monovalent cations was calculated and compared with the experimental values. The calculated concentration of the hard divalent cations (Ca2+, Mg2+), which suppressed the effect of the hard monovalent cations (K+, Na+), agreed with the experimental concentration. The same relations were obtained between the suppressive effect of a soft divalent and a soft monovalent cation. The chemical adsorption of Ag+ on the lateral-line organ of Xenopus laevis was investigated by using a transmission electron microscope equipped with an X-ray microprobe analyser in order to get further confirmation of this model. Silver applied to the lateral-line organ was found around a kinocilium but not in the hair cells of the lateral-line organ. Thus chemical adsorption of the cation on the surface of the receptor membrane was directly proved.

Animals

Electrical potentials of the subtectorial space in the guinea pig cochlea.

Precipitation of cobalt ions and iontophoretic marking by Alcian Blue were utilized in examination of physiological properties of the subtectorial space in the guinea pig cochlea. Cobalt ions injected into the scala media were sulfurated and observed as a black precipitation in cross sections. Precipitation was seen on the upper and the lower surface of the tectorial membrane, and on the reticular membrane. Alcian Blue was the most suitable dye for marking in the organ of Corti. Recording sites of potentials in the subtectorial space were identified by Alcian Blue marking. The potentials were similar to those measured in the scala media. These facts verify that the subtectorial space communicates with the scala media through the outermost margin of the tectorial membrane. Thus the sensory hairs of hair cells are bathed in the endolymph of high potassium concentration, and the condition for optimum sensitivity of their receptor function is maintained.

Alcian Blue

The receptive mechanism of various metallic ions in the lateral-line organ of the tadpoles of Rana catesbeiana.

The stimulating effect on the receptor organ of various mono-and divalent metallic ions on the lateral-line nerve of tadpoles was studied. The orders of the effectiveness were Ag + greater than T1+ greater than K+==Na+ greater than Li for monovalent ions and Sr2+ greater than Mg2+ greater than or equal too Ba2+ greater than Cd2+ greater than or equal too Co2+ greater than Mn2+ greater than Zn2+ for divalent ions. Both agree well with the order of Pearson's softness parameter for monovalent ions and Edwards' modified parameter for divalent ones. All sorts of divalent cations exhibited suppressive effects on the stimulating effect of the monovalent cations when they were applied together with the monovalent cations. A simple selection rule was found for the suppressive effect. The stimulating effect of Na+ or K+ was suppressed by all sorts of divalent cations. But the effect of Ag+ was suppressed by Cd2+, but not by Mg2+ nor by Ca2+. In order to remove the Ag+ effect, a dilute solution of DTT was used, although the effect of K+ or Na+ was removed easily by rinsing with distilled water. From these results the receptive mechanism of the endorgan was thought to be chemical adsorption of ions in the receptor cell membrane. Based on the principle of "hard and soft acid and base", it is suggested that there are two types of binding sites for the ions on the membrane, a soft site and a hard one.

Action Potentials